3I0N

Structure of the S. pombe Nbs1 FHA/BRCT-repeat domain

3I0N の概要

• エントリーDOI: 10.2210/pdb3i0n/pdb
• 関連するPDBエントリー: 3I0M
• 分子名称: DNA repair and telomere maintenance protein nbs1, GLYCEROL (3 entities in total)
• 機能のキーワード: nbs1, fha, brct-repeat, dna-damage, chromosomal protein, dna damage, dna repair, nucleus, phosphoprotein, telomere, gene regulation, cell cycle
• 由来する生物種: Schizosaccharomyces pombe (Fission yeast)
• 細胞内の位置: Nucleus: O43070
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 74583.64

構造登録者

Clapperton, J.A.,Lloyd, J.,Chapman, J.R.,Jackson, S.P.,Smerdon, S.J. (登録日: 2009-06-25, 公開日: 2009-10-13, 最終更新日: 2023-11-01)

主引用文献

Lloyd, J.,Chapman, J.R.,Clapperton, J.A.,Haire, L.F.,Hartsuiker, E.,Li, J.,Carr, A.M.,Jackson, S.P.,Smerdon, S.J.
A supramodular FHA/BRCT-repeat architecture mediates Nbs1 adaptor function in response to DNA damage
Cell(Cambridge,Mass.), 139:100-111, 2009

PubMed Abstract: The Mre11/Rad50/Nbs1 protein complex plays central enzymatic and signaling roles in the DNA-damage response. Nuclease (Mre11) and scaffolding (Rad50) components of MRN have been extensively characterized, but the molecular basis of Nbs1 function has remained elusive. Here, we present a 2.3A crystal structure of the N-terminal region of fission yeast Nbs1, revealing an unusual but conserved architecture in which the FHA- and BRCT-repeat domains structurally coalesce. We demonstrate that diphosphorylated pSer-Asp-pThr-Asp motifs, recently identified as multicopy docking sites within Mdc1, are evolutionarily conserved Nbs1 binding targets. Furthermore, we show that similar phosphomotifs within Ctp1, the fission yeast ortholog of human CtIP, promote interactions with the Nbs1 FHA domain that are necessary for Ctp1-dependent resistance to DNA damage. Finally, we establish that human Nbs1 interactions with Mdc1 occur through both its FHA- and BRCT-repeat domains, suggesting how their structural and functional interdependence underpins Nbs1 adaptor functions in the DNA-damage response.

PubMed: 19804756
DOI: 10.1016/j.cell.2009.07.043

実験手法

X-RAY DIFFRACTION (2.3 Å)